Batizi Benedek, Pollák Patrik, Dancsó András, Keglevich Péter, Simig Gyula, Volk Balázs, Milen Mátyás
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary.
Egis Pharmaceuticals Plc., Directorate of Drug Substance Development, P. O. Box 100, Keresztúri út 30-38, H-1475 Budapest, Hungary.
Beilstein J Org Chem. 2025 May 20;21:955-963. doi: 10.3762/bjoc.21.79. eCollection 2025.
A new total synthesis of the β-carboline alkaloid brevicarine is disclosed. The synthesis was carried out starting from an aromatic triflate key intermediate, allowing the introduction of various substituents into position 4 of β-carboline by cross-coupling reactions. Thanks to its scalability, this novel approach ensures a broad accessibility to the target compound for potential pharmacological measurements. Using detailed NMR studies, the NMR signals have been assigned for both the base and its dihydrochloride salt for further confirming their structures. A new synthesis of the related alkaloid brevicolline was also attempted from the same intermediate. However, after successful coupling of β-carboline with -methylpyrrole, the trials to saturate the pyrrole ring under various conditions led to unexpected reactions: reduction of ring A of the β-carboline skeleton or trifluoroethylation of the pyrrole moiety occurred, leading to interesting and potentially useful derivatives.
本文报道了一种新的β-咔啉生物碱短叶卡林的全合成方法。该合成从一种芳香三氟甲磺酸酯关键中间体开始，通过交叉偶联反应可将各种取代基引入β-咔啉的4位。由于其可扩展性，这种新方法确保了目标化合物在潜在药理学研究中的广泛可及性。通过详细的核磁共振研究，已对该碱及其二盐酸盐的核磁共振信号进行了归属，以进一步确认其结构。还尝试从相同中间体出发合成相关生物碱短叶柯林。然而，在β-咔啉与N-甲基吡咯成功偶联后，在各种条件下使吡咯环饱和的试验导致了意外反应：β-咔啉骨架的A环还原或吡咯部分的三氟乙基化发生，从而得到了有趣且可能有用的衍生物。
